JPS6353468A - Distribution of test specimen and instrument for same - Google Patents

Abstract

PURPOSE:To increase a pipetter capacity accuracy and correctly collect the trace quantity of a test specimen by once diluting the test specimen and the collecting part of the diluted specimen by weighting as a sample for an analysis. CONSTITUTION:A turn table type sampler 2 and a table 3 for reaction and measurement are provided in the specimen distributor 1 of an automatic analyzer and both the sampler 2 and the table 3 are intermittently rotated about rotating shafts in directions shown by arrows 4 and 5, respectively. Test specimen container holding openings 6 and mixing container holding openings 7 are formed in the sampler 2 so that the rows 8 and 9 the openings 6 and 7, respectively, are concentric. A test specimen container 10 and a mixing container 11 are made to the same size and the openings 6 and 7 are formed to the same diameter. Further, a reaction containers 13 are formed on the table 3 in a line along a reaction line 12 and the arm 15 of a pipetter 14 is rotatably provided about a shaft 16 between the sampler 12 are the table 3. A suction and discharge nozzle 17 is moved on moving part 35 by the rotation of the arm 15.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial Application Fields The present invention is applicable to blood, plasma, serum, lymph, etc. body fluids such as urine, excretions such as urine, secretions such as gastric juice, pancreatic juice, bile, saliva, sweat, etc.
The present invention relates to an automatic chemical analysis method and apparatus for specimens such as ascitic fluid, hydrodynamic fluid, paracentesis fluid, etc., and particularly relates to a specimen dispensing method and apparatus in an automatic chemical analysis method and apparatus for specimens.

The present invention also relates to a sample analysis method and apparatus, particularly a liquid chromatography analysis method, a 70-indiexian analysis method, and other trace sample analysis methods, a sample collection method in these apparatuses, and a sample collection apparatus such as an autosampler. .

(b) Conventional technology The component analysis values of samples such as blood and serum can be used to diagnose various diseases,
It is used for determining the disease status and therapeutic effects, and for treatment guidelines.

Moreover, such medical information is multi-item and requires high analytical accuracy in order to improve diagnostic accuracy. However, the amount of specimens such as blood that can be collected is limited, especially from patients and infants, and furthermore, to reduce running costs due to reagents, the amount of specimens handled by automatic chemical analyzers is extremely small. It has become

Such miniaturization of the amount of sample has been achieved through the development of enzyme reagents with excellent selectivity and sensitivity and improvements in pipettes, and, for example, the amount of sample per analysis item has reached several microliters.

(c) Problems to be solved by the invention However, depending on the analysis items, for example, glucose, urea nitrogen, albumin, etc., it is necessary to further improve the selectivity and sensitivity of the enzyme reagent. Although the amount of sample can be further reduced, the pipettor has not been sufficiently improved, and therefore accuracy cannot be ensured for sample amounts of several microliters or less. However, the advantages of developing new reagents with excellent selectivity and sensitivity have not been fully utilized.

The present invention aims to solve the problems associated with the lack of precision of pipetters in conventional automatic analyzers.

(d) 1,000 steps to solve the problem The present invention does not have to deal with the lack of precision of the pipettor,
The present invention provides an automatic chemical analyzer that can fully take advantage of the advantages of developing new reagents.

That is, the present invention collects a sample and a diluent into a pipettor channel in an amount corresponding to a target dilution ratio, and flows out the sample and diluted solution from a nozzle part of the channel into a container. , a sample dispensing method characterized by mixing a sample and a diluent, collecting a predetermined amount of the diluted sample from the container into a pipetter channel, and introducing the sample into a sample introduction section of an analysis system. Further, the present invention provides at least a sampler having a sample container holding part, a reaction line having a reaction container holding part, and a part that is movable (at least movable in a vertical direction) between the sampler and the reaction line. In a sample dispensing device equipped with a pipetter having a nozzle section that communicates with a plurality of metering pumps via channels, the sampler has a pipette at a first movement stop position of the nozzle of the pipettor where the pipettor performs a sample suction operation. A sample container holding section is provided, and the pipetter performs a discharging operation of the sample and diluent at the lower end of the movement path of the pipetter's nozzle with respect to the sample container holding section, and subsequent suction of the diluted sample. A mixing container holder is disposed at a second movement stop position of the nozzle of the pipetter that performs the operation, and the movement path of the pipetter nozzle is connected to the second downstream reaction line with respect to this second movement stop position. The sample dispensing device is characterized in that a reaction container holding section is disposed at a third movement stop position of the pipetter, where the pipettor performs a discharging operation of the diluted sample.

In the present invention, the sample and the diluent are collected together in the flow path of the pipettor in an amount according to a predetermined dilution ratio.
Since the sample and diluent collected in this flow path are not sufficiently mixed, in the present invention, the diluted sample is mixed by first draining the sample into a mixing container and then mixing the diluted sample with the diluted liquid. Collect a predetermined amount of the sample and introduce it into the analysis system. Therefore, in the present invention, the amount of the sample collected into the analysis system can be made much smaller than the amount of sample collected from the sample container in the vibrator. Furthermore, in the present invention, even if the sample is diluted so that the concentration of the component to be analyzed falls within the appropriate measurement range, the amount of the diluted sample sent to the reaction system can be within the optimum range.

In the present invention, diluting the sample to ensure that the concentration of the component to be analyzed falls within the appropriate measurement range may be performed only at the dilution stage using a pipettor for collecting the specimen and diluent.
The process consists of two stages: a dilution stage using a pipettor to collect the specimen and diluent, and a stage in which the diluted specimen is collected with a pipettor and introduced into the specimen introduction part of the analysis system, such as the specimen dispensing part or the sample introduction part. You can also do this. In this case, the same pipettor may be used for the two stages, or two pipetters may be used for each stage. Therefore, for example, one can be used as a pipettor exclusively for dilution, and the other can be used as an autosampler such as a chromatography analyzer or a 70-injection device.

As described above, the pipettor used in the present invention is capable of aspirating and discharging the sample and diluent, respectively, and a conventional pipettor is sufficient. The vibrator is equipped with pipettor pumps for aspirating and discharging specimens and for aspirating and discharging diluted liquid.

If the amount of sample to be collected and the amount of diluent to be collected are about the same, the standard pipettor pump is sufficient due to the volume accuracy of the pipettor pump, but if the dilution ratio is high, due to the volume accuracy of the pipettor pump, Preferably, two pipettor pumps are used, each having a different capacity.

In the present invention, reaction vessels may be arranged or moved in any form in the reaction line as long as the reaction line can carry out the necessary reaction for quantitative or qualitative analysis of the components. Therefore, a conventional reaction line such as a discrete type such as a batch type or a centrifugal type, or a fixed type or a rack type can be employed. The sampler is equipped with a sample container holding part and a mixing container holding part,
The mixing container holder is provided above and below the moving path of the nozzle of the pipettor with respect to the specimen container holder so that the sample collected from the specimen container can be easily discharged.

However, it is preferable to provide the nozzle adjacent to and around the sample container holder in view of the movement of the nozzle and the space available.

In the present invention, the operations performed via the nozzle of the pipetter are performed in the following order: suction collection of the specimen, outflow of the collected specimen and diluent, suction collection of the diluted specimen, and collection of the collected diluted specimen. A nozzle movement path is formed corresponding to the order of the nozzle operations. All of these nozzle operations are performed when the nozzle is stopped, so the nozzle is operated at the stop position.

Therefore, in the present invention, the sample suction sampling operation is performed at the first stop position of the nozzle. The suction operation of the diluted liquid is performed according to the amount of sampled liquid or according to the wave path switching operation, and is performed at the latest until the nozzle reaches the second stop position. At the second stop position of the nozzle, first, a discharge operation of the sampled sample and diluent is performed, and then a suction and collection operation of the diluted sample is performed. At the third stop position of the nozzle, a discharge operation of the diluted sample into the reaction vessel takes place. When the pipettor pump is divided into two units, the second stop position of the nozzle can be set so that the operating position of each nozzle can be separated.

It is preferable that the size of the mixing container be approximately the same as the size of the sample container, since this facilitates processing.

Of course, it can be made into an appropriate size depending on the degree of dilution.

(E) Effect The present invention is to dilute a sample once and then collect a part of the diluted sample as a sample for analysis, which reduces the amount of sample collected without increasing the volume accuracy of the pipettor pump. It can be performed.

In addition, in the present invention, since the sample container and the mixing container are arranged in the sampler, the nozzle of the pipetter is connected to the sample collection position and the mixing 11! By stopping at at least two of the eight sample collection positions, it is possible to easily reduce the amount of sample collected.

(F) Example Hereinafter, an example of an embodiment of the liquid sample collection method of the present invention will be explained with reference to the accompanying drawings.However, the present invention is not limited in any way by the following description. It's not something you can do.

FIG. 2 is a schematic partial plan view showing an example of applying the present invention to a specimen dispensing section of an automatic analysis device as an example of -Zn of the present invention, and FIG. 2 is a flow path diagram thereof. It is.

The sample dispensing section 1 of the automatic analyzer is equipped with a turntable type sampler 2 and a turntable type reaction/measurement table 3, both of which are connected to a rotating shaft (+'iT is also not shown). ) intermittently rotates in the directions of arrows 4 and 5. These one lin-deficient movement steps are carried out so as to move to the container in which + is placed.

The sampler 2 is formed with a hole 6 for holding the sample container 2 and a mixing container holding hole 7, and a row 8 of the sample container holding hole 6 and a row 9 of the mixing container holding hole 7 are formed concentrically. ing.

In this example, since the sample container 10 and the mixing container 11 are both formed to have the same dimensions, the sample container holding hole 6 and the mixing container holding hole 7 are formed to have the same diameter. Further, in this example, the mixing container holding hole 7 is located between the two sample container holding holes 6, corresponding to the trajectory of the nozzle.

On the reaction and measurement table 3, reaction vessels 13 are arranged in a line along the reaction line 12.

An arm 15 of a pipetter 14 is provided between the sampler 2 and the reaction/measurement table 3 so as to be rotatable about a shaft 16 . A suction and discharge nozzle 17 is attached to the tip of the arm 15, and its upper end 18 connects to the pipe line 1.
It is connected to a sample pipettor pump 20 via 9.

The sample pipettor pump 20 sucks and discharges a sample by reciprocating the piston 21. The sill 22 of the sample pipettor pump 20 is provided with a hole passage 23,
This hole path 23 is connected to a first flow path 26 of a three-way solenoid valve 25 via a conduit 24 .

Of the remaining two flow paths 27 and 28 of the three-way solenoid valve, the second flow path 27 is connected to a diluent pipettor pump 29, and the third flow path 28 is connected to a diluent pipettor pump 29. It is connected to the conduit 30. A filter 31 is attached to the tip of the conduit 30 and is immersed in a diluent 33 in a diluent container 32 .

In this example, the diluent bipeft bomb 29 sucks and discharges the diluent as the piston 34 reciprocates.

The suction/discharge nozzle 17 is moved along the movement path 35 indicated by the chain PQ by the pipettor 14's 7-m15 movement.
I] do it. Therefore, the sample container holding hole 6 of the sampler 2
The sampler 2 and the reaction and measurement table 3 rotate intermittently so that the reaction vessels 13 lined up in the mixing vessel holding hole 7 and the reaction line 12 stop at a position on this movement path 35.

A cleaning tank 36 in the form of a bath is provided at a predetermined location of the pipetter 14 and the f hyperactive path 35 of the pipettor 14 and the discharge nozzle 17 at the opening of the measurement table 3 for the sampler 2 and the reaction 1. In this example, when cleaning the nozzle, the diluted liquid 33 is collected by suction, so that the diluted liquid can be suctioned when the cleaning I (! supply pump (not shown) is pushed out).
The cleaning liquid supply pump and the diluting liquid pipettor pump 29 are arranged in opposite directions, and the operations of the pistons are connected and synchronized.

Since the present example is configured as described above, when the suction/discharge nozzle 17 is in the cleaning position d, the piston 34 of the diluted liquid pipettor pump 29 performs a suction operation. On the other hand, the suction/discharge nozzle 17 descends and immerses its tip in the cleaning tank to clean the outer periphery of the nozzle.Then, the cleaning liquid supply valve is closed, and the cleaning liquid supply pump starts supplying the cleaning liquid. 6 On the other hand, the diluted liquid pipettor pump discharges the diluted liquid and cleans the inside of the discharge nozzle 17 during suction 4 .

When cleaning of the suction and discharge nozzle 17 is completed, raise the nozzle 17, rotate the arm 15, move the nozzle 17 from the cleaning position onto the sample container 10, and then remove the nozzle 7 from the cleaning position. The specimen is lowered, the specimen pipette pump 20 is activated, and suction collection of the specimen from the specimen container 10 is started. During this time, the diluent Viventa Bomb 29
For example, the diluent 33 of 1904 is collected by suction by the suction operation of the piston 3.t. Sample pipettor pump 2
When, for example, 10 samples have been collected by suction, the suction and discharge nozzle 17 is raised, the arm 15 is rotated, and the specimen is transferred from the position of the specimen container 10 to the mixing container 11.
the nozzle 17. Therefore, the three-way solenoid 025 is activated to connect the channels from the two diluted liquid pipettor pumps to the first flow path, and the diluted liquid bippet bomb 29 is operated to discharge the diluted liquid. , into the sill 22 of the sample pipettor pump 20. The sample collected in the syringe 22 is sent to the suction and discharge nozzle 17 together with the diluent, but following the discharge operation of the two pipettor pumps for the diluent, the 7
By discharging the sample pipettor pump 20, the sample 190. diluted solution of iI and 1
The entire amount of the sample No. 04 is discharged into the mixing container 11, and the sample is mixed with a diluent to dilute it. The sample diluted 610 times is then sucked and collected by the sample pipettor 20. A sample of 10 d is collected by suction into the discharge nozzle 17 .

After collecting the diluted sample by suction, the suction and discharge nozzle 17
Raise the arm 15, rotate the arm 15 in the opposite direction to position the nozzle 17 above the reaction container 13 at the dispensing position on the reaction line, lower it, and start the pipettor pump 20 for discharging the sample. Then, the 10H diluted sample is dispensed into the reaction container.

In this example, the amount of sample collected in the reaction container 13 is
Although it corresponds to 1g, high capacity accuracy can be maintained.

In this example, the dilution rate was set to 10 times, but by further increasing the dilution rate, it is possible to ensure even higher volumetric accuracy and collect a much smaller amount of sample, reducing the amount of reagent consumed fil to the sample. It can be reduced according to the amount.

The device of this example can contain, for example, gluten, urea nitrogen, albumin, globulin, uric acid, creatine, creatinine,
It can be widely used for analyzing samples such as serum, plasma, and urine for alkaline phosphatase 7γ-tase and other biochemical analysis items.

(G) Effects of the Invention The present invention is to dilute a specimen once and then weigh and collect a portion of the diluted specimen as a sample for analysis.
A small amount of sample can be collected accurately without increasing pipettor capacity accuracy.

Therefore, according to the present invention, it is possible to collect a trace amount of a sample that exceeds the volume accuracy of a pipettor, which was difficult with conventional pipetting methods, and it is possible to analyze a desired trace amount within the appropriate measurement concentration range, thereby improving analytical accuracy. Towards. Therefore, according to the present invention, as compared to an automatic analysis method that employs a conventional sample dispensing method, the analysis accuracy is improved, and the amount of reagent consumed due to the small amount of samples t and + is reduced. It is possible to reduce the power r″C by reducing the amount of power required, thereby reducing analysis costs.

Further, the present invention can be used, for example, in a conventional automatic analyzer.
By providing a 71L alignment position on the sampler used and arranging the sample container and mixing container, the capacity of the reaction container can be reduced, and compared to conventional automatic analyzers, the reaction and measurement table is The number of anti-J6 containers can be increased. Therefore, it is possible to increase the amount of samples processed by the automatic analyzer, and moreover, no particular space is required.

(margin below)

[Brief explanation of drawings]

FIG. 1 is a schematic partial F-side view showing an example in which the present invention is applied to a sample dispensing section of an automatic analyzer as an embodiment of the present invention. It is a road map. Regarding the symbols in the figure, 1 is the sample dispensing unit, 2 is the sampler, 31 is the soil reaction and measurement table, 4 and 5 are arrows, 6 is the sample container holding hole, 7 is the mixing container holding hole, 8 is the sample Row of container holding holes, 9 is a row of mixing container holding holes, 10 is a sample container, 11 is a mixing container, 12 is a reaction line, 13 is a reaction container, 1 = 4 is a pipettor, 15 is an arm, 16 is a shaft ,
17 is a suction and discharge nozzle, 18 is the upper end of the nozzle, 1
9. 24 and 30 are pipes, 20 is a sample pipettor pump, 21 and 34 are pistons, 22 is a shilling, 23 is a hole path, 25 is a three-way solenoid valve, 26 is a first flow path, and 27 is a second flow path. 28 is the third flow 3828, 29 is the pipette pump for the 8 dilution solution, 31 is the filter, 32 is the diluent container, 33
3S is a diluent, 3S is a moving path, and 36 is a cleaning tank. Figure 1

Claims (3)

[Claims] (1) Collect the sample and diluted liquid into the pipettor channel in an amount corresponding to the desired dilution ratio, and flow out the sample and diluted solution from the nozzle of the channel into the container. A sample dispensing method comprising mixing a diluent, collecting a predetermined amount of the diluted sample from the container into a pipettor channel, and introducing the sample into a sample introduction section of an analysis system. (2) At least a sampler having a sample container holding part, a reaction line having a reaction container holding part, at least movable between the sampler and the reaction line, and also movable in the vertical direction, and a plurality of metering pumps. In a sample dispensing device including a pipetter having a nozzle portion communicating with the sampler through a flow path, the sampler includes a sample container holding portion disposed at a first movement stop position of the nozzle of the pipetter where the pipetter aspirates the sample. A pipettor nozzle that is installed at a lower position on the movement path of the pipetter nozzle with respect to the sample container holding part, and the pipettor performs a discharge operation of the sample and diluent and a suction operation of the diluted sample following this operation. A mixing container holder is disposed at a second movement stop position of the pipetter, and a reaction line downstream of the pipetter nozzle movement path with respect to the second movement stop position is provided with a mixing vessel holder. A sample dispensing device characterized in that a reaction container holder is disposed at a third movement stop position of a pipetter that performs a discharging operation of a sample. (3) A first pipettor and a second pipettor are provided, the first pipettor is movable at least between a first movement stop position and a second movement stop position of the pipettor, and the second pipettor is movable between a first movement stop position and a second movement stop position of the pipettor. The sample dispensing device according to claim 2, wherein the pipetter is movable between at least a second movement stop position and a third movement stop position.